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PLoS Genetics

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https://www.readbyqxmd.com/read/29161263/the-nucleoid-as-a-scaffold-for-the-assembly-of-bacterial-signaling-complexes
#1
Audrey Moine, Leon Espinosa, Eugenie Martineau, Mutum Yaikhomba, P J Jazleena, Deborah Byrne, Emanuele G Biondi, Eugenio Notomista, Matteo Brilli, Virginie Molle, Pananghat Gayathri, Tâm Mignot, Emilia M F Mauriello
The FrzCD chemoreceptor from the gliding bacterium Myxococcus xanthus forms cytoplasmic clusters that occupy a large central region of the cell body also occupied by the nucleoid. In this work, we show that FrzCD directly binds to the nucleoid with its N-terminal positively charged tail and recruits active signaling complexes at this location. The FrzCD binding to the nucleoid occur in a DNA-sequence independent manner and leads to the formation of multiple distributed clusters that explore constrained areas...
November 21, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/29161261/mrna-processing-in-mutant-zebrafish-lines-generated-by-chemical-and-crispr-mediated-mutagenesis-produces-unexpected-transcripts-that-escape-nonsense-mediated-decay
#2
Jennifer L Anderson, Timothy S Mulligan, Meng-Chieh Shen, Hui Wang, Catherine M Scahill, Frederick J Tan, Shao J Du, Elisabeth M Busch-Nentwich, Steven A Farber
As model organism-based research shifts from forward to reverse genetics approaches, largely due to the ease of genome editing technology, a low frequency of abnormal phenotypes is being observed in lines with mutations predicted to lead to deleterious effects on the encoded protein. In zebrafish, this low frequency is in part explained by compensation by genes of redundant or similar function, often resulting from the additional round of teleost-specific whole genome duplication within vertebrates. Here we offer additional explanations for the low frequency of mutant phenotypes...
November 21, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/29155828/role-of-co-repressor-genomic-landscapes-in-shaping-the-notch-response
#3
Stephen K K Chan, Gustavo Cerda-Moya, Robert Stojnic, Kat Millen, Bettina Fischer, Silvie Fexova, Lenka Skalska, Maria Gomez-Lamarca, Zoe Pillidge, Steven Russell, Sarah J Bray
Repressors are frequently deployed to limit the transcriptional response to signalling pathways. For example, several co-repressors interact directly with the DNA-binding protein CSL and are proposed to keep target genes silenced in the absence of Notch activity. However, the scope of their contributions remains unclear. To investigate co-repressor activity in the context of this well defined signalling pathway, we have analysed the genome-wide binding profile of the best-characterized CSL co-repressor in Drosophila, Hairless, and of a second CSL interacting repressor, SMRTER...
November 20, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/29155818/snail1-mediated-downregulation-of-foxa-proteins-facilitates-the-inactivation-of-transcriptional-enhancer-elements-at-key-epithelial-genes-in-colorectal-cancer-cells
#4
Sabine Jägle, Hauke Busch, Vivien Freihen, Sven Beyes, Monika Schrempp, Melanie Boerries, Andreas Hecht
Phenotypic conversion of tumor cells through epithelial-mesenchymal transition (EMT) requires massive gene expression changes. How these are brought about is not clear. Here we examined the impact of the EMT master regulator SNAIL1 on the FOXA family of transcription factors which are distinguished by their particular competence to induce chromatin reorganization for the activation of transcriptional enhancer elements. We show that the expression of SNAIL1 and FOXA genes is anticorrelated in transcriptomes of colorectal tumors and cell lines...
November 20, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/29155813/post-guidance-signaling-by-extracellular-matrix-associated-slit-slit-n-maintains-fasciculation-and-position-of-axon-tracts-in-the-nerve-cord
#5
Krishna Moorthi Bhat
Axon-guidance by Slit-Roundabout (Robo) signaling at the midline initially guides growth cones to synaptic targets and positions longitudinal axon tracts in discrete bundles on either side of the midline. Following the formation of commissural tracts, Slit is found also in tracts of the commissures and longitudinal connectives, the purpose of which is not clear. The Slit protein is processed into a larger N-terminal peptide and a smaller C-terminal peptide. Here, I show that Slit and Slit-N in tracts interact with Robo to maintain the fasciculation, the inter-tract spacing between tracts and their position relative to the midline...
November 20, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/29155810/regulation-of-transcription-elongation-in-response-to-osmostress
#6
Andrea Silva, Santiago Cavero, Victoria Sarah, Carme Solé, René Böttcher, Sebastián Chávez, Francesc Posas, Eulàlia de Nadal
Cells trigger massive changes in gene expression upon environmental fluctuations. The Hog1 stress-activated protein kinase (SAPK) is an important regulator of the transcriptional activation program that maximizes cell fitness when yeast cells are exposed to osmostress. Besides being associated with transcription factors bound at target promoters to stimulate transcriptional initiation, activated Hog1 behaves as a transcriptional elongation factor that is selective for stress-responsive genes. Here, we provide insights into how this signaling kinase functions in transcription elongation...
November 20, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/29149188/orienting-the-causal-relationship-between-imprecisely-measured-traits-using-gwas-summary-data
#7
Gibran Hemani, Kate Tilling, George Davey Smith
Inference about the causal structure that induces correlations between two traits can be achieved by combining genetic associations with a mediation-based approach, as is done in the causal inference test (CIT). However, we show that measurement error in the phenotypes can lead to the CIT inferring the wrong causal direction, and that increasing sample sizes has the adverse effect of increasing confidence in the wrong answer. This problem is likely to be general to other mediation-based approaches. Here we introduce an extension to Mendelian randomisation, a method that uses genetic associations in an instrumentation framework, that enables inference of the causal direction between traits, with some advantages...
November 17, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/29145394/unc-16-jip3-regulates-early-events-in-synaptic-vesicle-protein-trafficking-via-lrk-1-lrrk2-and-ap-complexes
#8
Bikash Choudhary, Madhushree Kamak, Neena Ratnakaran, Jitendra Kumar, Anjali Awasthi, Chun Li, Ken Nguyen, Kunihiro Matsumoto, Naoki Hisamoto, Sandhya P Koushika
JIP3/UNC-16/dSYD is a MAPK-scaffolding protein with roles in protein trafficking. We show that it is present on the Golgi and is necessary for the polarized distribution of synaptic vesicle proteins (SVPs) and dendritic proteins in neurons. UNC-16 excludes Golgi enzymes from SVP transport carriers and facilitates inclusion of specific SVPs into the same transport carrier. The SVP trafficking roles of UNC-16 are mediated through LRK-1, whose localization to the Golgi is reduced in unc-16 animals. UNC-16, through LRK-1, also enables Golgi-localization of the μ-subunit of the AP-1 complex...
November 16, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/29140975/natural-variation-of-a-sensor-kinase-controlling-a-conserved-stress-response-pathway-in-escherichia-coli
#9
Manuela Roggiani, Srujana S Yadavalli, Mark Goulian
Previous studies have shown that exponentially growing Escherichia coli can detect mild acidity (~pH 5.5) and, in response, synthesize enzymes that protect against severe acid shock. This adaptation is controlled by the EvgS/EvgA phosphorelay, a signal transduction system present in virtually every E. coli isolate whose genome has been sequenced. Here we show that, despite this high level of conservation, the EvgS/EvgA system displays a surprising natural variation in pH-sensing capacity, with some strains entirely non-responsive to low pH stimulus...
November 15, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/29136647/katanin-like-2-katnal2-functions-in-multiple-aspects-of-haploid-male-germ-cell-development-in-the-mouse
#10
Jessica E M Dunleavy, Hidenobu Okuda, Anne E O'Connor, D Jo Merriner, Liza O'Donnell, Duangporn Jamsai, Martin Bergmann, Moira K O'Bryan
The katanin microtubule-severing proteins are essential regulators of microtubule dynamics in a diverse range of species. Here we have defined critical roles for the poorly characterised katanin protein KATNAL2 in multiple aspects of spermatogenesis: the initiation of sperm tail growth from the basal body, sperm head shaping via the manchette, acrosome attachment, and ultimately sperm release. We present data suggesting that depending on context, KATNAL2 can partner with the regulatory protein KATNB1 or act autonomously...
November 14, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/29131815/the-karrikin-receptor-kai2-promotes-drought-resistance-in-arabidopsis-thaliana
#11
Weiqiang Li, Kien Huu Nguyen, Ha Duc Chu, Chien Van Ha, Yasuko Watanabe, Yuriko Osakabe, Marco Antonio Leyva-González, Mayuko Sato, Kiminori Toyooka, Laura Voges, Maho Tanaka, Mohammad Golam Mostofa, Motoaki Seki, Mitsunori Seo, Shinjiro Yamaguchi, David C Nelson, Chunjie Tian, Luis Herrera-Estrella, Lam-Son Phan Tran
Drought causes substantial reductions in crop yields worldwide. Therefore, we set out to identify new chemical and genetic factors that regulate drought resistance in Arabidopsis thaliana. Karrikins (KARs) are a class of butenolide compounds found in smoke that promote seed germination, and have been reported to improve seedling vigor under stressful growth conditions. Here, we discovered that mutations in KARRIKIN INSENSITIVE2 (KAI2), encoding the proposed karrikin receptor, result in hypersensitivity to water deprivation...
November 13, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/29140986/correction-kinesin-1-promotes-chondrocyte-maintenance-during-skeletal-morphogenesis
#12
Adrian Santos-Ledo, Marina Garcia-Macia, Philip D Campbell, Marta Gronska, Florence L Marlow
[This corrects the article DOI: 10.1371/journal.pgen.1006918.].
November 2017: PLoS Genetics
https://www.readbyqxmd.com/read/29121639/a-subset-of-sweet-sensing-neurons-identified-by-ir56d-are-necessary-and-sufficient-for-fatty-acid-taste
#13
John M Tauber, Elizabeth B Brown, Yuanyuan Li, Maria E Yurgel, Pavel Masek, Alex C Keene
Fat represents a calorically potent food source that yields approximately twice the amount of energy as carbohydrates or proteins per unit of mass. The highly palatable taste of free fatty acids (FAs), one of the building blocks of fat, promotes food consumption, activates reward circuitry, and is thought to contribute to hedonic feeding underlying many metabolism-related disorders. Despite a role in the etiology of metabolic diseases, little is known about how dietary fats are detected by the gustatory system to promote feeding...
November 2017: PLoS Genetics
https://www.readbyqxmd.com/read/29121637/the-combinatorial-control-of-alternative-splicing-in-c-elegans
#14
June H Tan, Andrew G Fraser
Normal development requires the right splice variants to be made in the right tissues at the right time. The core splicing machinery is engaged in all splicing events, but which precise splice variant is made requires the choice between alternative splice sites-for this to occur, a set of splicing factors (SFs) must recognize and bind to short RNA motifs in the pre-mRNA. In C. elegans, there is known to be extensive variation in splicing patterns across development, but little is known about the targets of each SF or how multiple SFs combine to regulate splicing...
November 2017: PLoS Genetics
https://www.readbyqxmd.com/read/29117179/a-mutation-in-the-viral-sensor-2-5-oligoadenylate-synthetase-2-causes-failure-of-lactation
#15
Samantha R Oakes, David Gallego-Ortega, Prudence M Stanford, Simon Junankar, Wendy Wing Yee Au, Zoya Kikhtyak, Anita von Korff, Claudio M Sergio, Andrew M K Law, Lesley E Castillo, Stephanie L Allerdice, Adelaide I J Young, Catherine Piggin, Belinda Whittle, Edward Bertram, Matthew J Naylor, Daniel L Roden, Jesse Donovan, Alexei Korennykh, Christopher C Goodnow, Moira K O'Bryan, Christopher J Ormandy
We identified a non-synonymous mutation in Oas2 (I405N), a sensor of viral double-stranded RNA, from an ENU-mutagenesis screen designed to discover new genes involved in mammary development. The mutation caused post-partum failure of lactation in healthy mice with otherwise normally developed mammary glands, characterized by greatly reduced milk protein synthesis coupled with epithelial cell death, inhibition of proliferation and a robust interferon response. Expression of mutant but not wild type Oas2 in cultured HC-11 or T47D mammary cells recapitulated the phenotypic and transcriptional effects observed in the mouse...
November 2017: PLoS Genetics
https://www.readbyqxmd.com/read/29108021/hippo-tgf-%C3%AE-and-src-mapk-pathways-regulate-transcription-of-the-upd3-cytokine-in-drosophila-enterocytes-upon-bacterial-infection
#16
Philip Houtz, Alessandro Bonfini, Xi Liu, Jonathan Revah, Aurélien Guillou, Mickael Poidevin, Korneel Hens, Hsin-Yi Huang, Bart Deplancke, Yu-Chen Tsai, Nicolas Buchon
Cytokine signaling is responsible for coordinating conserved epithelial regeneration and immune responses in the digestive tract. In the Drosophila midgut, Upd3 is a major cytokine, which is induced in enterocytes (EC) and enteroblasts (EB) upon oral infection, and initiates intestinal stem cell (ISC) dependent tissue repair. To date, the genetic network directing upd3 transcription remains largely uncharacterized. Here, we have identified the key infection-responsive enhancers of the upd3 gene and show that distinct enhancers respond to various stresses...
November 2017: PLoS Genetics
https://www.readbyqxmd.com/read/29107996/epigenetic-memory-via-concordant-dna-methylation-is-inversely-correlated-to-developmental-potential-of-mammalian-cells
#17
Minseung Choi, Diane P Genereux, Jamie Goodson, Haneen Al-Azzawi, Shannon Q Allain, Noah Simon, Stan Palasek, Carol B Ware, Chris Cavanaugh, Daniel G Miller, Winslow C Johnson, Kevin D Sinclair, Reinhard Stöger, Charles D Laird
In storing and transmitting epigenetic information, organisms must balance the need to maintain information about past conditions with the capacity to respond to information in their current and future environments. Some of this information is encoded by DNA methylation, which can be transmitted with variable fidelity from parent to daughter strand. High fidelity confers strong pattern matching between the strands of individual DNA molecules and thus pattern stability over rounds of DNA replication; lower fidelity confers reduced pattern matching, and thus greater flexibility...
November 2017: PLoS Genetics
https://www.readbyqxmd.com/read/29107990/long-lasting-masculinizing-effects-of-postnatal-androgens-on-myelin-governed-by-the-brain-androgen-receptor
#18
Charly Abi Ghanem, Cindy Degerny, Rashad Hussain, Philippe Liere, Antoine Pianos, Sophie Tourpin, René Habert, Wendy B Macklin, Michael Schumacher, Abdel M Ghoumari
The oligodendrocyte density is greater and myelin sheaths are thicker in the adult male mouse brain when compared with females. Here, we show that these sex differences emerge during the first 10 postnatal days, precisely at a stage when a late wave of oligodendrocyte progenitor cells arises and starts differentiating. Androgen levels, analyzed by gas chromatography/tandem-mass spectrometry, were higher in males than in females during this period. Treating male pups with flutamide, an androgen receptor (AR) antagonist, or female pups with 5α-dihydrotestosterone (5α-DHT), revealed the importance of postnatal androgens in masculinizing myelin and their persistent effect into adulthood...
November 2017: PLoS Genetics
https://www.readbyqxmd.com/read/29099833/how-convincing-is-a-matching-y-chromosome-profile
#19
Mikkel M Andersen, David J Balding
The introduction of forensic autosomal DNA profiles was controversial, but the problems were successfully addressed, and DNA profiling has gone on to revolutionise forensic science. Y-chromosome profiles are valuable when there is a mixture of male-source and female-source DNA, and interest centres on the identity of the male source(s) of the DNA. The problem of evaluating evidential weight is even more challenging for Y profiles than for autosomal profiles. Numerous approaches have been proposed, but they fail to deal adequately with the fact that men with matching Y-profiles are related in extended patrilineal clans, many of which may not be represented in available databases...
November 2017: PLoS Genetics
https://www.readbyqxmd.com/read/29095827/co-option-of-the-bzip-transcription-factor-vrille-as-the-activator-of-doublesex1-in-environmental-sex-determination-of-the-crustacean-daphnia-magna
#20
Nur Syafiqah Mohamad Ishak, Quang Dang Nong, Tomoaki Matsuura, Yasuhiko Kato, Hajime Watanabe
Divergence of upstream regulatory pathways of the transcription factor Doublesex (Dsx) serves as a basis for evolution of sex-determining mechanisms in animals. However, little is known about the regulation of Dsx in environmental sex determination. In the crustacean Daphnia magna, environmental sex determination is implemented by male-specific expression of the Dsx ortholog, Dsx1. Transcriptional regulation of Dsx1 comprises at least three phases during embryogenesis: non-sex-specific initiation, male-specific up-regulation, and its maintenance...
November 2017: PLoS Genetics
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